The need for fast-track, high-quality and low-cost studies about the role of the BCG vaccine in the fight against COVID-19

• Letter to the Editor
• Open Access
• 
  

• Marcos Pereira, 
• Enny Paixão, 
• Anete Trajman, 
• Ramon Andrade de Souza, 
• Marcio Santos da Natividade, 
• Julia M. Pescarini, 
• Susan Martins Pereira, 
• Florisneide Rodrigues Barreto, 
• Ricardo Ximenes, 
• Margareth Dalcomo, 
• Maria Yury Ichihara, 
• Ceuci Nunes, 
• Manoel Barral-Netto & 
• Maurício L. Barreto 

Respiratory Research volume 21, Article number: 178 (2020) 

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Abstract

Bacillus Calmette-Guérin (BCG) vaccination is routine and near-universal in many low- and middle-income countries (LMIC). It has been suggested that BCG can have a protective effect on COVID-19 morbidity and mortality. This commentary discusses the limitations of the evidence around BCG and COVID-19. We argue that higher-quality evidence is necessary to understand the protective effect of the BCG vaccine from existing, secondary data, while we await results from clinical trials currently conducted in different settings.

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Genetic polymorphisms in vitamin D pathway influence 25(OH)D levels and are associated with atopy and asthma

• Research
• Open Access

Allergy, Asthma & Clinical Immunology

• Alana Alcântara Galvão, 
• Flávia de Araújo Sena, 
• Emília Maria Medeiros de Andrade Belitardo, 
• Maria Borges Rabelo de Santana, 
• Gustavo Nunes de Oliveira Costa, 
• Álvaro Augusto Cruz, 
• Maurício Lima Barreto, 
• Ryan dos Santos Costa, 
• Neuza Maria Alcantara-Neves & 
• Camila Alexandrina Figueiredo 

Allergy, Asthma & Clinical Immunology volume 16, Article number: 62 (2020) 

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Abstract

Background

Vitamin D deficiency or insufficiency, has been associated with atopy and lack of asthma control. Our objective was to investigate associations between variants in genes of vitamin D pathway with serum levels of 25-hydroxyvitamin D (25(OH)D), atopy, asthma and asthma severity in teenagers from Northeast Brazil.

Distinct type 2-high inflammation associated molecular signatures of chronic rhinosinusitis with nasal polyps with comorbid asthma

• Research
• Open Access
• 
  

Ming Wang, 

Xiangting Bu, 

Ge Luan, 

Liqing Lin, 

Yang Wang, 

Jianmin Jin, 

Luo Zhang & 

Chengshuo Wang 

Clinical and Translational Allergy volume 10, Article number: 26 (2020)

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Abstract

Background

Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and comorbid asthma have more severe disease and are difficult to treat. However, the molecular endotypes associated with CRSwNP with comorbid asthma (CRSwNP + AS) are not clear. This study aimed to investigate the characteristics of type 2 inflammation and the molecular signatures associated with CRSwNP + AS.

Methods

A total of 195 subjects; including 65 CRSwNP + AS patients, 99 CRSwNP-alone patients, and 31 healthy control subjects; were enrolled in the study. Nasal tissues from patients with CRSwNP + AS, CRSwNP-alone and control subjects were assessed for infiltration of inflammatory cells and concentrations of total IgE. Whole-transcriptome sequencing was performed and differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs) and their associated pathways were analyzed. The correlations between type 2 cytokines and local eosinophils, tissue IgE, and transcriptome signatures were evaluated.

Results

Differentially expressed genes and pathways between CRSwNP + AS
and CRSwNP-alone. a Volcano plots illustrating DE-mRNAs of
CRSwNP + AS versus CRSwNP-alone identified by RNA sequencing.
b Top 15 KEGG pathways (blue column) and top 5 BioCarta pathways
(turquoise column) significantly enriched by DE-mRNAs.
c The expression of arachidonic acid metabolism-related DE-mRNAs
between CRSwNP + AS and CRSwNP-alone.
The colour coding of heat maps represents the gene expression
level normalized to Control group, calculated based on fragments
per kilo-base of exon per million fragments mapped (FPKM).
Yellow box indicates the up-regulated genes in CRSwNP + AS group.
d The expression of critical cytokines and their receptors that indicated
the activity of different inflammatory endotypes.
Yellow stars represent significantly differentially expressed
genes between CRSwNP + AS and CRSwNP-alone.
P < 0.05 were considered statistically significant. CRSwNP chronic rhinosinusitis
with nasal polyps, AS asthma, DE differentially expressed,
KEGG Kyoto Encyclopedia of Genes and Genomes

Significantly higher local eosinophil infiltration and higher levels of total IgE were found in nasal tissues from CRSwNP + AS patients than in nasal tissues from CRSwNP-alone patients. Furthermore, atopy and recurrence were significantly more frequent in patients with CRSwNP + AS than in patients with CRSwNP-alone (62.5% vs 28.6% and 66.7% vs 26.9%, respectively). RNA sequencing analysis identified 1988 common DE-mRNAs, and 176 common DE-lncRNAs shared by CRSwNP + AS versus control and CRSwNP-alone versus control. Weighted gene coexpression network analysis (WGCNA) identified LINC01146 as hub lncRNA dysregulated in both subtypes of CRSwNP. Overall, 968 DE-mRNAs and 312 DE-lncRNAs were identified between CRSwNP + AS and CRSwNP-alone. Both pathway enrichment analysis and WGCNA indicated that the phenotypic traits of CRSwNP + AS were mainly associated with higher activities of arachidonic acid metabolism, type 2 cytokines related pathway and fibrinolysis pathway, and lower activity of IL-17 signalling pathway. Furthermore, the expression of type 2 cytokines; IL5 and IL13, was positively correlated with local eosinophil infiltration, tissue IgE level, and the expression of DE-mRNAs that related to arachidonic acid metabolism. Moreover, WGCNA identified HK3-006 as hub lncRNA in yellow module that most positively correlated with phenotypic traits of CRSwNP + AS.

Conclusions

Patients with CRSwNP + AS have distinct type 2-high inflammation-associated molecular signatures in nasal tissues compared to patients with CRSwNP-alone.

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Open AccessArticle

Elucidation of Inverse Agonist Activity of Bilastine

by Hiroyuki Mizuguchi ^1,*,Tomoharu Wakugawa ²,Hisato Sadakata ³,Seiichiro Kamimura ⁴,Mai Takemoto ¹,Tomomi Nakagawa ¹,Masami Yabumoto ⁵,Yoshiaki Kitamura ⁴,Noriaki Takeda ⁴ andHiroyuki Fukui ^4,5

¹

Laboratory of Pharmacology Faculty of Pharmacy Osaka Ohtani University, Osaka 584-8540, Japan

²

Department of Molecular Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8505, Japan

³

TIMELAPS VISION INC., Saitama 353-0004, Japan

⁴

Department of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8505, Japan

⁵

Medical Corporation Kinshukai, Osaka 558-0011, Japan

^*

Author to whom correspondence should be addressed.

Pharmaceutics 2020, 12(6), 525; https://doi.org/10.3390/pharmaceutics12060525

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Abstract

H₁-antihistamines antagonize histamine and prevent it from binding to the histamine H₁ receptor (H1R). Some of them also act as inverse agonists, which are more potent than pure antagonists because they suppress the constitutive H1R activity. Bilastine is a non-sedative antihistamine which is one of the most satisfy the requirements for oral antihistamines. However, there is no information to show the inverse agonist activity of bilastine including inositol phosphates accumulation, and its inverse agonist activity is yet to be elucidated. Here we evaluated whether bilastine has inverse agonist activity or not. Intracellular calcium concentration was measured using Fluo-8. Inositol phosphates accumulation was assayed using [³H]myo-inositol. The H1R mRNA level was measured using real-time RT-PCR. At rest, Ca²⁺ oscillation was observed, indicating that H1R has intrinsic activity. Bilastine attenuated this fluorescence oscillation. Bilastine suppressed the increase in IPs formation in a dose-dependent manner and it was about 80% of the control level at the dose of 3 μM. Bilastine also suppressed histamine-induced increase in IPs formation to the control level. Furthermore, bilastine suppressed basal H1R gene expression in a dose-dependent manner. Data suggest that bilastine is an inverse agonist. Preseasonal prophylactic administration with bilastine could down-regulate basal H1R gene expression in the nasal mucosa and ameliorate the nasal symptoms during the peak pollen period. View Full-Text

Keywords: H₁-antihistamines; histamine H₁ receptor gene expression; inositol phosphates accumulation; inverse agonist; time-laps Ca²⁺ imaging

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Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Sensitization to storage proteins in peanut and hazelnut is associated with higher levels of inflammatory markers in asthma

• Research
• Open Access
• Clinical and Molecular Allergy

• Jennifer Johnson, 
• Andrei Malinovschi, 
• Jonas Lidholm, 
• Carl Johan Petersson, 
• Lennart Nordvall, 
• Christer Janson, 
• Kjell Alving & 
• Magnus P. Borres 

Clinical and Molecular Allergy volume 18, Article number: 11 (2020) 

• details

Abstract

Background

Sensitization to peanuts and hazelnuts is common among young asthmatics and can be primary or a result of cross-reactivity. Sensitization as a result of cross-reactivity to birch pollen is typically associated to tolerance or mild and local symptoms upon intake of peanut or hazelnut.

Aim

The aim of this study was to investigate relationships between IgE antibody responses against peanut and hazelnut components, airway and systemic inflammation markers, lung function parameters and reported food hypersensitivity in a cohort of asthmatic children and young adults.